Until recently, it was unclear if people could attain control over specific neural processes to influence their associated perceptions, cognitions and behaviors. Using real-time fMRI (rtfMRI) neurofeedback, we recently demonstrated that healthy subjects and patients with chronic pain can learn to control activity in the anterior cingulate cortex, leading to significant and clinically meaningful reductions in their pain. We propose to extend this exciting finding to patients with chronic low back pain (CLBP). CLBP is a highly prevalent and difficult to treat condition with a pressing need for novel therapies. Although underlying mechanisms in CLBP are not well understood, basic science has revealed that abnormalities in central pain modulatory and emotion regulatory systems play a crucial role. At the same time, a robust clinical literature suggests the value of mind-body therapies (MBTs) and cognitive/emotion regulatory strategies in the management of chronic pain. What is not clear is how the basic and clinical science findings are linked, such that MBTs alter the functioning of the brain systems involved in pain. This project proposes to use rtfMRI neurofeedback as an innovative technique to manipulate key brain systems related to pain and then translate mechanistic findings to optimize clinical therapies for chronic pain. We will advance this critical area by resolving three issues identified in our previous rtfMRI studies: (1) because patients employ different cognitive strategies to modulate brain activity, their activated brain regions and efficacy in learned control vary, (2) multiple brain regions are activated and deactivated during single region feedback control, suggesting control of multiple, distributed regions may be more effective than control of a single region, and (3) significant individual differences exist in how well patients can modulate their brain activity. Therefore, our overall aims are to: (1) characterize CLBP patients' cognitive strategies for optimally controlling single and multiple distributed brain regions, and (2) identify mediators of pain relief due to rtfMRI. Our overall objective is to advance our scientific knowledge of mind-body therapies, specifically how learned control of specific neural processes leads to reduction in chronic pain.